A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest?

Cancer Research Group, Facultat de Biologia, Departament de Bioquímica i Biomedicina Molecular, Universitat de BarcelonaBarcelona, Spain.

2

Institut de Biomedicina de la Universitat de BarcelonaBarcelona, Spain.

3

Facultat de Biologia, Departament de Genètica, Microbiologia i Estadística, Universitat de BarcelonaBarcelona, Spain.

4

Abbott NutritionGranada, Spain.

Abstract

Bed rest has been an established treatment in the past prescribed for critically illness or convalescing patients, in order to preserve their body metabolic resource, to prevent serious complications and to support their rapid path to recovery. However, it has been reported that prolonged bed rest can have detrimental consequences that may delay or prevent the recovery from clinical illness. In order to study disuse-induced changes in muscle and bone, as observed during prolonged bed rest in humans, an innovative new model of muscle disuse for rodents is presented. Basically, the animals are confined to a reduced space designed to restrict their locomotion movements and allow them to drink and eat easily, without generating physical stress. The animals were immobilized for either 7, 14, or 28 days. The immobilization procedure induced a significant decrease of food intake, both at 14 and 28 days of immobilization. The reduced food intake was not a consequence of a stress condition induced by the model since plasma corticosterone levels -an indicator of a stress response- were not altered following the immobilization period. The animals showed a significant decrease in soleus muscle mass, grip force and cross-sectional area (a measure of fiber size), together with a decrease in bone mineral density. The present model may potentially serve to investigate the effects of bed-rest in pathological states characterized by a catabolic condition, such as diabetes or cancer.

Immobilization model. (A) Representative pictures of immobilized rats and control rat in a standard cage. Each immobilization cage is able to host two animals and it is equipped (in its upper part) with a grating to dispose food and water. (B) Schematic representation of the immobilization tested model. The cage had a reduction in volume of 80% in relation with control standard cage. The arrow indicated the housing area of a single rat.